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Cell reports

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Disease-specific suppressive granulocytes participate in glioma progression

Published:3 December 2024 DOI: 10.1016/j.celrep.2024.115014 PMID: 39630582
Jiarui Zhao,?Di Wu,?Jiaqi Liu,?Yang Zhang,?Chunzhao Li,?Weichen Zhao,?Penghui Cao,?Shixuan Wu,?Mengyuan Li,?Wenlong Li,?Ying Liu,?Yingying Huang,?Ying Cao,?Yiwen Sun,?Ence Yang,?Nan Ji,?Jing Yang,?Jian Chen

Abstract

Glioblastoma represents one of the most aggressive cancers, characterized by severely limited therapeutic options. Despite extensive investigations into this brain malignancy, cellular and molecular components governing its immunosuppressive microenvironment remain incompletely understood. Here, we identify a distinct neutrophil subpopulation, termed disease-specific suppressive granulocytes (DSSGs), present in human glioblastoma and lower-grade gliomas. DSSGs exhibit the concurrent expression of multiple immunosuppressive and immunomodulatory signals, and their abundance strongly correlates with glioma grades and poor clinical outcomes. Genetic disruption of neutrophil recruitment in immunocompetent mouse models of gliomas, achieved through Cxcl1 knockout in glioma cells or host-specific Cxcr2 deletion or diphtheria toxin A-mediated neutrophil depletion, can significantly enhance antitumor immunity and prolong survival. Further, we reveal that the skull bone marrow and meninges can be the primary sources of neutrophils and DSSGs in human and mouse glioma tumors. These findings demonstrate a critical mechanism underlying the establishment of the immunosuppressive microenvironment in gliomas.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
D(+)-Glucose 50-99-7 C6H12O6 1121 suppliers $6.00-$26950.00
HEPES 7365-45-9 C8H18N2O4S 747 suppliers $6.00-$17250.00
Sodium pyruvate 113-24-6 C3H5NaO3 669 suppliers $13.00-$884.00
Streptomycin sulfate 3810-74-0 C21H41N7O16S 627 suppliers $15.00-$1880.00
Penicillin G sodium salt 69-57-8 C16H17N2NaO4S 464 suppliers $15.60-$672.68
Trypsin 9002-07-7 C35H47N7O10 456 suppliers $17.70-$24930.00
Deoxyribonuclease 9003-98-9 NULL 290 suppliers $58.00-$2170.00
BLASTICIDIN S HYDROCHLORIDE 3513-03-9 C17H27ClN8O5 148 suppliers $40.00-$1008.00

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